Healthy Volunteers, Immunogenicity
Conditions
Keywords
Pegfilgrastim, Biosimilar, Immunogenicity, Pharmacokinetics, Pharmacodynamics, Safety, Healthy Volunteers
Brief summary
The study was an assessor-blind, balanced, parallel, randomized, two-treatment, comparative immunogenicity study of multiple doses of subcutaneous (SC) Pegfilgrastim injection (6 mg/0.6 mL; Intas Pharmaceuticals Ltd. proposed biosimilar INTP5 compared to innovator product, US-Neulasta) in healthy, adult, human subjects under fed conditions.
Interventions
COMBINATION_PRODUCTINTP5
INTP5, a pegfilgrastim biosimilar to US Neulasta.
COMBINATION_PRODUCTUS Neulasta
US Neulasta: FDA approved pegfilgrastim innovator product.
Sponsors
Lambda Therapeutic Research Ltd.
Intas Pharmaceuticals, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
The study staff taking care of subject's safety and the laboratory personnel doing the sample analysis of PK, PD, and immunogenicity data were blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Normal, healthy adult human volunteers between 18 to 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India. 2. Having body weight ≥50 kg and body mass index (BMI) between 18.5 and 29.9 (both inclusive), calculated as weight in kg/height in meter\^2. 3. Not having any significant disease in medical history or clinically significant abnormal findings during screening, abdominal ultrasonography, medical history, clinical examination, laboratory evaluations, 12-lead echocardiogram (ECG) and chest X-ray (posterior-anterior view; within the last 6 months) recordings. 4. Able to understand and comply with the study procedures, in the opinion of the investigator. 5. Able to give voluntary written informed consent for participation in the trial. 6. In case of female subjects: * Surgically sterilized at least 6 months prior to study participation; Or If a woman of child bearing potential is willing to use a suitable and effective double barrier contraceptive method or intra uterine device during the study. * Serum pregnancy test (for female subjects) must be negative.
Exclusion criteria
1. Known hypersensitivity to the study drug or its constituents and/or hypersensitivity to E. coli derived proteins, and/or previous exposure to the study drug. 2. History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system. 3. Known case of hereditary fructose intolerance. 4. Subjects with latex allergies will be excluded as the needle cover on the single-use prefilled syringe contains dry natural rubber (latex). 5. Any clinically significant laboratory finding including absolute neutrophil count (ANC), platelet, red blood cells (RBC) count, and hemoglobin level at the time of screening. 6. Prior exposure to any peptide colony stimulating or growth factor, including erythropoietin, filgrastim or Pegfilgrastim; Prior exposure to any vaccines, immunoglobulin preparations or immunomodulators within the past 6 months prior to receiving first dose; evidence of E. coli diarrhea or diseases within 3 months. 7. Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAIDs induced urticaria. 8. Subjects with a history of pulmonary infiltrate or pneumonia in the last 6 months. 9. History of any hematologic disease including sickle cell disorders. 10. Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose. 11. Receipt of over-the-counter medicines which have not yet cleared from the body (5 half-lives must have passed for the medicine to be considered to have cleared from the body). 12. A recent history of harmful use of alcohol, i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.) or consumption of alcohol or alcoholic products within 72 hours prior to receiving study medicine. 13. Smokers, who smoke 10 or more than 10 cigarettes/day or inability to abstain from smoking during the study. 14. Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans. 15. Donation of blood (1 unit or 350 mL) or equivalent amount of blood substitute. 16. Receipt of an investigational medicinal product or participation in a drug research study within a period of 90 days prior to the first dose of study medication. Elimination half-life of the study drug should be taken into consideration for inclusion of the subject in the study. 17. Positive result for human immunodeficiency virus (HIV I &/or II) and/or hepatitis B and C tests. 18. History or presence of cancer because of which anticipated life span is less than 5 years as per the investigator's assessment. 19. History or presence of psychiatric disorders. 20. Presence of tattoo or scars or any type of skin lesions due to infection, burning, wound or inflammation at the proposed site of injection. 21. An unusual diet, for whatever reason (e.g. low-sodium), for 4 weeks prior to receiving the study medicine. In any such case, subject selection will be at the discretion of the Principal Investigator. 22. Consumption of grape fruit or grape fruit products within 72 hours prior to receiving study drug. 23. A history of difficulty in donating blood. 24. Females, pregnant or lactating, or planning to become pregnant during the time the subject is on study or found positive in pregnancy test at screening. 25. Any infections in the last 4 weeks before receiving study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose. | Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Endpoints: Pegfilgrastim AUC[0-t] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | Area under the serum concentration vs. time curve, calculated by linear trapezoidal rule from measured data points from the time zero to the time of last quantified concentration. |
| PK Endpoints: Pegfilgrastim AUC[0-∞] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | Area under the serum concentration versus time curve from time zero to infinity. Where AUC\[0-infinity\]= AUC\[0-t\] + Ct/lambda-z, Ct is the last measurable concentration and lamda-z is the terminal rate constant. AUC\[0-infinity\] is the sum of measurable and extrapolated parts. |
| PK Endpoints: Pegfilgrastim T[Max] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects. |
| PK Endpoints: Pegfilgrastim λz (Lambda-z) | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | Terminal rate constant: First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more nonzero plasma concentration values. |
| PK Endpoints: Pegfilgrastim R^2 Adjusted | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz (lambda-z). R\^2 is the coefficient of determination and can range from 0 to 1, with higher values indicating greater predictability. |
| PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\[0-t\])/AUC\[0-infinity\]\] x 100. |
| PK Endpoints: Pegfilgrastim t[1/2] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | The terminal half-life calculated using the formula 0.693/(lambda-z) |
| PK Endpoints: Pegfilgrastim C[Max] | Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration. | Pharmacokinetic (PK) properties of the test and reference formulations were assessed by measuring serum Pegfilgrastim concentration. Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects. |
| PD Endpoints for Baseline Non-adjusted ANC: T[Max] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method. |
| PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Time to reach the maximum measured absolute neutrophil count (ANC) |
| PD Endpoints for Baseline Adjusted ANC: E[Max] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Maximum measured absolute neutrophil count (ANC). |
| PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method. |
| PD Endpoints for Baseline Adjusted ANC: T[Max] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Time to reach the maximum measured absolute neutrophil count (ANC) |
| PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more non-zero plasma concentration values. |
| PD Endpoints for Baseline Adjusted ANC: t[1/2] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | The terminal half-life will be calculated as 0.693/(lambda-z) |
| PD Endpoints for Baseline Non-adjusted ANC: E[Max] | Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration. | Maximum measured absolute neutrophil count (ANC). |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| INTP5 Biosimilar Product INTP5 subcutaneously at a dose of 6 mg/0.6 mL.
INTP5: A pegfilgrastim biosimilar to US Neulasta. | 100 |
| US Neulasta Reference Product US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.
US Neulasta: FDA approved pegfilgrastim innovator product. | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Medical Grounds | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 |
Baseline characteristics
| Characteristic | US Neulasta Reference Product | Total | INTP5 Biosimilar Product |
|---|---|---|---|
| Age, Continuous | 34.3 years STANDARD_DEVIATION 6.05 | 32.9 years STANDARD_DEVIATION 6.58 | 31.5 years STANDARD_DEVIATION 6.82 |
| BMI | 24.51 kg/m^2 STANDARD_DEVIATION 3.266 | 24.23 kg/m^2 STANDARD_DEVIATION 3.173 | 23.95 kg/m^2 STANDARD_DEVIATION 3.069 |
| Height | 160.1 cm STANDARD_DEVIATION 8.68 | 160.2 cm STANDARD_DEVIATION 8.56 | 160.2 cm STANDARD_DEVIATION 8.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 100 Participants | 200 Participants | 100 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 100 Participants | 200 Participants | 100 Participants |
| Sex: Female, Male Female | 40 Participants | 80 Participants | 40 Participants |
| Sex: Female, Male Male | 60 Participants | 120 Participants | 60 Participants |
| Weight | 62.6 kg STANDARD_DEVIATION 7.49 | 61.9 kg STANDARD_DEVIATION 7.92 | 61.3 kg STANDARD_DEVIATION 8.31 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 1 / 100 |
| other Total, other adverse events | 32 / 100 | 37 / 100 |
| serious Total, serious adverse events | 0 / 100 | 1 / 100 |
Outcome results
Primary
Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.
Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.
Time frame: Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| INTP5 Biosimilar Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | Positive for Anti-Drug-Antibody | 10 Participants |
| INTP5 Biosimilar Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | Positive in Neutralizing Anti-Drug-Antibody | 0 Participants |
| INTP5 Biosimilar Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | No Anit-Drug Antibody Confirmed Positive Results | 84 Participants |
| US Neulasta Reference Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | Positive for Anti-Drug-Antibody | 9 Participants |
| US Neulasta Reference Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | Positive in Neutralizing Anti-Drug-Antibody | 0 Participants |
| US Neulasta Reference Product | Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies. | No Anit-Drug Antibody Confirmed Positive Results | 91 Participants |
Secondary
PD Endpoints for Baseline Adjusted ANC: AUEC[0-t]
Area under the absolute neutrophil count (ANC) versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 4920.26 x10^3cells*h/uL | Standard Deviation 1339.674 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 4967.86 x10^3cells*h/uL | Standard Deviation 1229.792 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 6539.58 x10^3cells*h/uL | Standard Deviation 2202.473 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 5992.49 x10^3cells*h/uL | Standard Deviation 1555.062 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 4389.55 x10^3cells*h/uL | Standard Deviation 1140.655 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 4578.32 x10^3cells*h/uL | Standard Deviation 1200.125 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 5441.01 x10^3cells*h/uL | Standard Deviation 1478.241 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 5676.92 x10^3cells*h/uL | Standard Deviation 1991.456 |
Secondary
PD Endpoints for Baseline Adjusted ANC: E[Max]
Maximum measured absolute neutrophil count (ANC).
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-NEGATIVE | 36.50 x10^3cells/uL | Standard Deviation 10.458 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-POSITIVE | 38.37 x10^3cells/uL | Standard Deviation 9.548 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-POSITIVE | 42.50 x10^3cells/uL | Standard Deviation 10.061 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-NEGATIVE | 40.80 x10^3cells/uL | Standard Deviation 11.038 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-NEGATIVE | 33.35 x10^3cells/uL | Standard Deviation 9.189 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-POSITIVE | 34.18 x10^3cells/uL | Standard Deviation 8.503 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-NEGATIVE | 36.56 x10^3cells/uL | Standard Deviation 8.755 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: E[Max] | ADA-POSITIVE | 40.76 x10^3cells/uL | Standard Deviation 17.17 |
Secondary
PD Endpoints for Baseline Adjusted ANC: t[1/2]
The terminal half-life will be calculated as 0.693/(lambda-z)
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-NEGATIVE | 62.25 h | Standard Deviation 28.847 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-POSITIVE | 67.03 h | Standard Deviation 41.296 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-POSITIVE | 69.72 h | Standard Deviation 25.447 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-NEGATIVE | 64.13 h | Standard Deviation 26.785 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-NEGATIVE | 77.23 h | Standard Deviation 86.239 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-POSITIVE | 81.74 h | Standard Deviation 29.981 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-POSITIVE | 67.02 h | Standard Deviation 22.706 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: t[1/2] | ADA-NEGATIVE | 76.02 h | Standard Deviation 59.888 |
Secondary
PD Endpoints for Baseline Adjusted ANC: T[Max]
Time to reach the maximum measured absolute neutrophil count (ANC)
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-NEGATIVE | 64.617 h | Standard Deviation 11.1482 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-POSITIVE | 72.003 h | Standard Deviation 0.0072 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-POSITIVE | 67.453 h | Standard Deviation 15.7091 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-NEGATIVE | 59.735 h | Standard Deviation 14.9546 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-NEGATIVE | 65.553 h | Standard Deviation 15.8887 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-POSITIVE | 64.002 h | Standard Deviation 12.0014 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-NEGATIVE | 65.043 h | Standard Deviation 20.661 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: T[Max] | ADA-POSITIVE | 61.461 h | Standard Deviation 29.9401 |
Secondary
PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z)
First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more non-zero plasma concentration values.
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-NEGATIVE | 0.01 h | Standard Deviation 0.007 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-POSITIVE | 0.01 h | Standard Deviation 0.006 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-POSITIVE | 0.01 h | Standard Deviation 0.003 |
| US Neulasta Reference Product | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-NEGATIVE | 0.01 h | Standard Deviation 0.006 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-NEGATIVE | 0.01 h | Standard Deviation 0.006 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-POSITIVE | 0.01 h | Standard Deviation 0.004 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-NEGATIVE | 0.01 h | Standard Deviation 0.006 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Adjusted ANC: λz (Lambda-z) | ADA-POSITIVE | 0.01 h | Standard Deviation 0.005 |
Secondary
PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t]
Time to reach the maximum measured absolute neutrophil count (ANC)
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Table breaks participants into ADA(-) or ADA(+), totaling the overall number of participants by arm. 5 Subjects having three consecutive missing samples in elimination phase were excluded from the analysis of AUEC0-t reducing the total participants to 88 for INTP5 Dose 1, 88 for INTP5 Dose 2, 92 for Neulasta Dose 1, and 91 for Neulasta Dose 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 7107.14 h*ng/mL | Standard Deviation 1481.971 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 7286.53 h*ng/mL | Standard Deviation 1744.737 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 8539.99 h*ng/mL | Standard Deviation 1522.935 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 7929.25 h*ng/mL | Standard Deviation 1561.246 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 6718.70 h*ng/mL | Standard Deviation 1361.957 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 6846.77 h*ng/mL | Standard Deviation 763.675 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-NEGATIVE | 7359.09 h*ng/mL | Standard Deviation 1455.57 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: AUEC[0-t] | ADA-POSITIVE | 7761.65 h*ng/mL | Standard Deviation 1658.478 |
Secondary
PD Endpoints for Baseline Non-adjusted ANC: E[Max]
Maximum measured absolute neutrophil count (ANC).
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-NEGATIVE | 40.72 x10^3cells/uL | Standard Deviation 10.862 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-POSITIVE | 42.89 x10^3cells/uL | Standard Deviation 10.512 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-POSITIVE | 46.53 x10^3cells/uL | Standard Deviation 9.093 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-NEGATIVE | 44.63 x10^3cells/uL | Standard Deviation 11.077 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-NEGATIVE | 38.34 x10^3cells/uL | Standard Deviation 9.925 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-POSITIVE | 38.38 x10^3cells/uL | Standard Deviation 8.211 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-NEGATIVE | 40.62 x10^3cells/uL | Standard Deviation 8.963 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: E[Max] | ADA-POSITIVE | 44.96 x10^3cells/uL | Standard Deviation 16.409 |
Secondary
PD Endpoints for Baseline Non-adjusted ANC: T[Max]
Area under the ANC versus time curve from time zero to the last measurable concentration as calculated by linear trapezoidal method.
Time frame: Venous blood samples (2 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) following 1st and 2nd dose administration.
Population: Outcome Measure Data Table is breaks participants into negative-ADA or positive-ADA, totaling the overall number of participants by arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-NEGATIVE | 64.710 h | Standard Deviation 11.1076 |
| INTP5 Biosimilar Product | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-POSITIVE | 72.003 h | Standard Deviation 0.0072 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-POSITIVE | 67.453 h | Standard Deviation 15.7091 |
| US Neulasta Reference Product | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-NEGATIVE | 59.587 h | Standard Deviation 14.917 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-NEGATIVE | 63.182 h | Standard Deviation 15.8763 |
| US Neulasta Dose 1 | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-POSITIVE | 64.002 h | Standard Deviation 12.0014 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-NEGATIVE | 64.637 h | Standard Deviation 20.5772 |
| US Neulasta Dose 2 | PD Endpoints for Baseline Non-adjusted ANC: T[Max] | ADA-POSITIVE | 61.461 h | Standard Deviation 29.9401 |
Secondary
PK Endpoints: Pegfilgrastim AUC[0-∞]
Area under the serum concentration versus time curve from time zero to infinity. Where AUC\[0-infinity\]= AUC\[0-t\] + Ct/lambda-z, Ct is the last measurable concentration and lamda-z is the terminal rate constant. AUC\[0-infinity\] is the sum of measurable and extrapolated parts.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim AUC[0-∞] | 22436.497 ng.h/mL | Standard Deviation 9922.4383 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim AUC[0-∞] | 13637.403 ng.h/mL | Standard Deviation 6699.9736 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim AUC[0-∞] | 16630.861 ng.h/mL | Standard Deviation 11253.7406 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim AUC[0-∞] | 15280.376 ng.h/mL | Standard Deviation 11058.1142 |
Secondary
PK Endpoints: Pegfilgrastim AUC[0-t]
Area under the serum concentration vs. time curve, calculated by linear trapezoidal rule from measured data points from the time zero to the time of last quantified concentration.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim AUC[0-t] | 22417.938 ng.h/mL | Standard Deviation 9922.2648 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim AUC[0-t] | 13640.695 ng.h/mL | Standard Deviation 6709.2752 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim AUC[0-t] | 16610.870 ng.h/mL | Standard Deviation 11255.1296 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim AUC[0-t] | 15255.327 ng.h/mL | Standard Deviation 11050.758 |
Secondary
PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs]
The residual area in percentage determined by the formula, \[(AUC\[0-infinity\]-AUC\[0-t\])/AUC\[0-infinity\]\] x 100.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] | 0.115 percentage of AUC | Standard Deviation 0.1106 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] | 0.644 percentage of AUC | Standard Deviation 1.4428 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] | 0.230 percentage of AUC | Standard Deviation 0.2672 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim AUC[_%Extrap_Obs] | 0.266 percentage of AUC | Standard Deviation 0.2664 |
Secondary
PK Endpoints: Pegfilgrastim C[Max]
Pharmacokinetic (PK) properties of the test and reference formulations were assessed by measuring serum Pegfilgrastim concentration. Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim C[Max] | 483.230 ng/mL | Standard Deviation 175.1787 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim C[Max] | 346.018 ng/mL | Standard Deviation 150.4879 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim C[Max] | 368.569 ng/mL | Standard Deviation 223.338 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim C[Max] | 371.778 ng/mL | Standard Deviation 263.444 |
Secondary
PK Endpoints: Pegfilgrastim R^2 Adjusted
Goodness of fit statistic for the terminal phase, adjusted for the number of points used in the estimation of λz (lambda-z). R\^2 is the coefficient of determination and can range from 0 to 1, with higher values indicating greater predictability.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim R^2 Adjusted | 0.968 Coefficient of Determination | Standard Deviation 0.0379 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim R^2 Adjusted | 0.876 Coefficient of Determination | Standard Deviation 0.133 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim R^2 Adjusted | 0.974 Coefficient of Determination | Standard Deviation 0.0245 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim R^2 Adjusted | 0.879 Coefficient of Determination | Standard Deviation 0.2339 |
Secondary
PK Endpoints: Pegfilgrastim t[1/2]
The terminal half-life calculated using the formula 0.693/(lambda-z)
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim t[1/2] | 36.721 h | Standard Deviation 11.0052 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim t[1/2] | 36.612 h | Standard Deviation 19.6215 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim t[1/2] | 34.172 h | Standard Deviation 8.8669 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim t[1/2] | 40.616 h | Standard Deviation 14.6054 |
Secondary
PK Endpoints: Pegfilgrastim T[Max]
The time of observing the peak concentration, calculated from the serum concentration vs. time profile of the individual subjects.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim T[Max] | 22.405 h | Standard Deviation 3.3758 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim T[Max] | 20.800 h | Standard Deviation 5.5936 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim T[Max] | 22.226 h | Standard Deviation 3.5298 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim T[Max] | 23.111 h | Standard Deviation 2.6667 |
Secondary
PK Endpoints: Pegfilgrastim λz (Lambda-z)
Terminal rate constant: First order rate constant associated with the terminal (log-linear) portion of the curve. This was estimated via linear regression of time vs. log concentration. This parameter was calculated by linear least squares regression analysis using last three or more nonzero plasma concentration values.
Time frame: Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.
Population: All the 19 ADA confirmed positive subjects were included in the PK analysis: 10 subjects from INTP5 and 9 subjects from US-Neulasta
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INTP5 Biosimilar Product | PK Endpoints: Pegfilgrastim λz (Lambda-z) | 0.021 1/h | Standard Deviation 0.0071 |
| US Neulasta Reference Product | PK Endpoints: Pegfilgrastim λz (Lambda-z) | 0.025 1/h | Standard Deviation 0.0142 |
| US Neulasta Dose 1 | PK Endpoints: Pegfilgrastim λz (Lambda-z) | 0.022 1/h | Standard Deviation 0.0058 |
| US Neulasta Dose 2 | PK Endpoints: Pegfilgrastim λz (Lambda-z) | 0.019 1/h | Standard Deviation 0.0074 |